A distinct role of CD4 ⁺ Th17- and Th17-stimulated CD8 ⁺ CTL in the pathogenesis of type 1 diabetes and experimental autoimmune encephalomyelitis

Both CD4 ⁺ Th17-cells and CD8 ⁺ cytotoxic T lymphocytes (CTLs) are involved in type 1 diabetes and experimental autoimmune encephalomyelitis (EAE). However, their relationship in pathogenesis of these autoimmune diseases is still elusive.We generated ovalbumin (OVA)- or myelin oligodendrocyte glycoprotein (MOG)- specific Th17 cells expressing RORγt and IL-17 by in vitro co-culturing OVA-pulsed and MOG _35-55 peptide-pulsed dendritic cells (DC _OVA and DC _MOG) with CD4 ⁺ T cells derived from transgenic OTII and MOG-T cell receptor mice, respectively. We found that these Th17 cells when transferred into C57BL/6 mice stimulated OVA- and MOG-specific CTL responses, respectively. To assess the above question, we adoptively transferred OVA-specific Th17 cells into transgenic rat insulin promoter (RIP)- mOVA mice or RIP-mOVA mice treated with anti-CD8 antibody to deplete Th17-stimulated CD8 ⁺ T cells. We demonstrated that OVA-specific Th17-stimulated CTLs, but not Th17 cells themselves, induced diabetes in RIPmOVA. We also transferred MOG-specific Th17 cells into C57BL/6 mice and H-2K ^b-/- mice lacking of the ability to generate Th17-stimulated CTLs. We further found that MOG-specific Th17 cells, but not Th17-activated CTLs induced EAE in C57BL/6 mice. Taken together, our data indicate a distinct role of Th17 cells and Th17-stimulated CTLs in the pathogenesis of TID and EAE, which may have great impact on the overall understanding of Th17 cells in the pathogenesis of autoimmune diseases.